Inorganic salts of sulfurous acid have heretofore been discovered by Jose Antonio Arias Alvarez to have anti-coagulant and antithrombotic properties, see U.S. Ser. No. 227,382 filed Jan. 22, 1981, now abandoned in favor of continuation-in-part application Ser. No. 271,850 filed June 6, 1981, now abandoneed in favor of copending application Ser. No. 337,176 filed Jan. 5, 1982.
Various carbonyl bisulfite adducts have heretofore been used for commercial purposes, such as control of mold in seeds. Glyoxal bisulfites have been used medically to inhibit blood platelet aggregation; glyoxals are 1,2-dicarbonyl compounds and the bisulfite adduct is used only as a carrier for the glyoxal. So far as is known these carbonyl bisulfite adducts have never heretofore been known to have anticoagulant or antithrombotic properties.
Anticoagulants and antithrombotics are a group of compounds with diversified pharmacologic actions, used in a variety of chemical thrombotic disorders. Thrombotic disorders are generally divided into venous thrombosis and arterial occlusive disorders. Venous thrombosis of the lower extremities is important because it can cause pulmonary embolism which may be fatal. Heparin and warfarin are commonly used in clinical medicine for prevention and treatment of deep venous thrombosis and pulmonary embolism. Their pharmacological actions are in the inhibition of blood coagulation activity (i.e., heparin) or of synthesis of coagulation factors (i.e., warfarin). Platelets play an important part in arterial thrombosis. Drugs that inhibit platelet aggregation are generally regarded as being potentially usefull for prophylactic therapy of arterial thrombotic disorders, including, for example, stroke, myorcardial infarction and peripheral vascular disease. Despite the availability of many agents which possess anti-platelet aggregating properties, only a few are currently under clinical trials (for example, aspirin, dipyridamole, sulfinpyrazone). None of these agents exhibit unequivocal efficacy. Compounds with more specific pharmacological action are urgently sought in order to provide better medical care for patients with these serious disorders.
An anti-platelet aggregatory agent is a substance which inhibits platelet aggregation.
An antithrombotic agent is a substance which inhibits formation or development of a thrombus (or thrombosis). For present patent purposes, it will be understood that the term "thrombus" or equivalent includes the subject matter of the term "embolus" unless otherwise specifically indicated. In general, an antithrombotic agent may display, in the presence of mammalian blood or appropriately prepared plasma, anticoagulant activity and/or anti-platelet aggregatory activity.